Search Results (694)

Alcohol-associated hepatitis (AH) is the most severe clinical manifestation of alcohol-associated liver disease. Corticosteroids are the only disease-specific therapy shown to improve short-term survival. Currently, no non-invasive markers are available to predict patient response to corticosteroids or long-term survival in AH. This study investigates whether surface antigens on plasma extracellular vesicles (EVs), key mediators of intercellular communication, can reflect the underlying immune dysregulation in AH and serve as prognostic markers. Patients with AH were prospectively enrolled between 2020 and 2024. Blood samples were collected before corticosteroid initiation during the first 24 h of hospitalization. EVs were characterized using nanoparticle tracking analysis, cryo-electron microscopy, and flow cytometry. Interleukin-6 (IL-6), soluble (s)CD62p, Circulating Vascular Cell Adhesion Molecule-1 (sVCAM), tumor necrosis factor receptor superfamily member 1 (TNRFS1a), and Intercellular Adhesion Molecule 1 (ICAM-1) were quantified by ELISA. Key outcome variables included response to corticosteroids and mortality. A total of 46 patients with AH and 28 healthy donors (HD) were included. EV concentration was significantly higher in AH patients than in HD (9.3 × 10¹¹ [IQR 4–24] versus 2.4 × 10¹¹ [IQR 2–4], p = 0.03). Specific EV antigens were associated with key clinical outcomes: CD20 and CD2 levels differed between patients with or without infections (bacterial, viral, and fungal) developed during hospitalization; CD40 and CD146 were elevated in patients who developed acute kidney injury. EVs enriched in monocyte (CD14) and T-reg (CD25) markers were associated with plasma IL-6 levels, while endothelial markers CD105 and CD146 correlated with sVCAM and sCD62p. EVs enriched in platelet (CD49e) and endothelial (CD31) markers were associated with corticosteroid response, whereas EVs enriched with endothelial (CD105 and CD146) and B lymphocyte (CD19) markers were associated with mortality. Overall, EVs enriched in endothelial and monocyte markers may represent a candidate non-invasive tool for predicting corticosteroid response and mortality in AH, aiding risk stratification and early identification of non-responders for timely transplant evaluation. Full article

Dextrin-based nanosponges (D-NS) are promising candidates for oral drug delivery due to their biocompatibility, mucoadhesive properties, and tunable swelling behavior. In this study, pH-sensitive nanosponges were synthesized using β-cyclodextrin (β-CD), GluciDex^®2 (GLU2), and KLEPTOSE^® Linecaps (LC) as building blocks, crosslinked with pyromellitic dianhydride (PMDA) and citric acid (CA). The nanosponges were mechanically size-reduced via homogenization and ball milling, and characterized by FTIR, TGA, dynamic light scattering (DLS), and zeta potential measurements. Swelling kinetics, cross-linking density (determined using Flory–Rehner theory), rheological behavior, and mucoadhesion were evaluated under simulated gastric and intestinal conditions. The β-CD:PMDA 1:4 NS was selected for drug studies due to its optimal balance of structural stability, swelling capacity (~863% at pH 6.8), and highest apomorphine (APO) loading (8.23%) with 90.58% encapsulation efficiency. All nanosuspensions showed favorable polydispersity index values (0.11–0.30), homogeneous size distribution, and stable zeta potentials, confirming suspension stability. Storage at 4 °C for six months revealed no changes in physicochemical properties or apomorphine (APO) degradation, indicating protection by the nanosponge matrix. D-NS exhibited tunable swelling, pH-responsive behavior, and mucoadhesive properties, with nanoparticle–mucin interactions quantified by the rheological synergism parameter (∆G′ = 53.45, ∆G″ = −36.26 at pH 6.8). In vitro release studies demonstrated slow, sustained release of APO from D-NS in simulated intestinal fluid compared to free drug diffusion, highlighting the potential of D-NS as pH-responsive, mucoadhesive carriers with controlled drug release and defined nanoparticle–mucin interactions. Full article

Background/Objectives: Inadequate characterization of protective antigens poses a significant challenge to the development of vaccines for African swine fever (ASF), particularly for antigen-dependent formulations such as subunit, mRNA, and recombinant viral vector vaccines. To address this, we aimed to screen African swine fever virus (ASFV) antigens and enhance their immunogenicity using a nanoparticle delivery platform. Methods: Here, six ASFV antigens (p30, p54, pE120R, pH124R, pE184L, and CD2v) were purified and used to immunize pigs individually. The effects of antibodies induced by these six antigens on ASFV replication or hemadsorption was evaluated in primary porcine alveolar macrophages (PAMs). These six antigens were, respectively, conjugated to ferritin via SpyTag/SpyCatcher to prepare six ferritin nanoparticles. A cocktail of the six mixed antigens or a cocktail of the six mixed nanoparticles was used to immunize pigs separately, and the differences in induced humoral and cellular immune responses were compared. Results: Antibodies generated against p30, p54, pE120R, pH124R, and pE184L in immunized pigs significantly inhibited ASFV replication in PAMs, while anti-CD2v antibodies specifically obstructed the hemadsorption of ASFV. Notably, immunization with a cocktail of these antigen-conjugated nanoparticles elicited a stronger virus-inhibitory antibody response compared to immunization with a cocktail of antigen monomers. Furthermore, nanoparticle immunization induced robust cellular immunity, evidenced by elevated serum IFN-γ, increased numbers of ASFV-specific IFN-γ-secreting cells, and an expanded CD8⁺ T cell population. Conclusions: Our study identifies a set of promising ASFV antigen candidates and demonstrates that ferritin nanoparticle delivery synergistically enhances both humoral and cellular immune responses against ASFV, providing a rational strategy for multi-antigen ASF vaccine design. Full article

This research aimed to assess the effect of chitosan nanoparticles (ChNPs) during in vitro shoot proliferation of vanilla using temporary immersion bioreactors (TIB). TIB culture is a biotechnological process that uses semiautomated containers for the production of explants exposed in liquid culture medium. Concentrations of control, 25, 50, 100, 200, and 400 mg/L ChNPs were evaluated in Murashige and Skoog culture medium. Morphological characterization of ChNPs was performed using scanning electron microscopy. At 60 days of culture, survival (%), development variables, photosynthetic pigment content, lipid peroxidation expressed in malondialdehyde, total phenolic content (TPC), hydrogen peroxide (H₂O₂) content, and total antioxidant capacity (TAC) expressed in trolox equivalents were evaluated. The data were analyzed with analysis of variance, with a Tukey test (p ≤ 0.05) using SPSS statistics software, version 29. The results revealed that the greatest survival (%) was obtained at concentrations of control, 25, and 50 mg/L ChNPs, while the lowest survival (%) was observed at concentrations of 400 mg/L ChNPs. Growth stimulation was found, as well as an increase in chlorophyll and β-carotene at concentrations of 25 and 50 mg/L ChNPs. The level of H₂O₂ increased at 25 and 50 mg/L ChNPs. Lipid peroxidation showed no differences among treatments. TPC increased at 100 and 200 mg/L ChNPs, while TAC increased at 200 and 400 mg/L ChNPs. In conclusion, the administration of ChNPs at low concentrations can stimulate growth, while at high concentrations they can inhibit it, a response known as hormesis or hormetic effect. Full article

The increasing presence of pharmaceutical residues such as ibuprofen in aquatic environments represents a growing concern due to their persistence and limited biodegradability. In this study, selenium-doped tin oxide (SnO₂:Se) nanoparticles covered with glycerol were synthesized via a microwave-assisted method to evaluate their photocatalytic performance in the degradation of ibuprofen under ultraviolet (UV) and visible light. Optimal synthesis parameters were determined at pH 7.5–8.0 and 130 °C, yielding stable, dark-brown colloidal suspensions. HRTEM analysis revealed a coexistence of one-dimensional (1D) nanowires and zero-dimensional (0D) quantum dots, confirming nanoscale morphology with crystallite sizes between 8 and 100 nm. EDS analysis confirmed the presence of Sn, O, and trace Se (0.1 wt%), indicating Se incorporation as a dopant. UV–Vis spectroscopy showed strong absorption near 324 nm and slight band-gap narrowing in the Se-doped samples, suggesting enhanced visible-light responsiveness. Photocatalytic experiments demonstrated an ibuprofen degradation efficiency of ~60% under visible light and 80% under UV irradiation with aeration, compared to only 5% removal using commercial SnO₂. The enhanced performance was attributed to Se-induced band-gap modulation, effective charge-carrier separation, and singlet oxygen generation. Full article

Wound dressing coverages (WDC) play a key role in protecting skin lesions and preventing infection. Polymeric membranes have been widely explored as WDC due to their ability to incorporate bioactive agents, including antimicrobial nanoparticles and non-steroidal anti-inflammatory drugs (NSAIDs). In this study, polycaprolactone (PCL)-based membranes functionalized with titanium dioxide nanoparticles (TiO₂ NPs) and ibuprofen (IBP) were fabricated using a film manufacturing approach, and their structural and biocompatibility profiles were evaluated. The membranes were characterized by SEM, FTIR and XPS. Bands at 1725 cm⁻¹, 2950 cm⁻¹, 2955 cm⁻¹, 2865 cm⁻¹ and 510 cm⁻¹ proved molecular stability of reagents during manufacture. In SEM, the control shows the flattest surface, while the PCL-IBP and PCL-IBP-TiO₂ NPs groups had increased rugosity. In vitro biocompatibility was evaluated using human fetal osteoblasts (hFOB). On day 3, the cell adhesion response of hFOB seeded in PCL-IBP and PCL-IBP-TiO₂ NPs groups showed the biggest absorbances (p = 0.0014 and p = 0.0491, respectively). On day 7 PCL-IBP group had lower lectin binding than the control (p = 0.007) and the PCL-IBP-TiO₂ NPs (p = 0.015) membranes, but no evidence of cytotoxicity was observed in any group. Furthermore, the Live/Dead test adds more biocompatibility evidence to conveniently discriminate between live and dead cells. The PCL polymeric membrane elaborated in this study may confer antiseptic, analgesic and anti-inflammatory properties, making these membranes ideal for skin lesions. Full article

Smart nanocarriers are being increasingly explored to improve the performance selectivity of cancer chemotherapy. Here, two pH-responsive magnetic nanocarriers were developed using quaternary chitosan (HTCC) functionalized with 3-(triethoxysilyl)propyl isocyanate- ICPTES (MNP-HTCC1) or 3-(glycidyloxypropyl)trimethoxysilane-GPTMS (MNP-HTCC2) to form hybrid silica shells on Fe₃O₄ cores. The resulting core–shell nanoparticles (14.5 and 12.5 nm) displayed highly positive zeta potentials (+45.4 to +27.1 mV, pH 4.2–9.5), confirming successful HTCC incorporation and strong colloidal stability. Both nanocarriers achieved high doxorubicin (DOX) loading at pH 9.5, reaching 90% efficiency and a capacity of 154 µg DOX per mg. DOX release was pH-dependent, with faster release under acidic conditions relevant to tumor and endo-lysosomal environments. At pH 4.2, MNP-HTCC1 released 90% of DOX over 72 h, while MNP-HTCC2 released 79%. Release at pH 5.0 was intermediate (67–72%), and moderate at physiological pH (43–55%). All formulations showed an initial burst followed by sustained release. Kinetic modelling (Weibull) indicated a diffusion-controlled mechanism consistent with Fickian transport through the HTCC–silica matrix. Cytotoxicity assays using MCF-7 breast cancer cells revealed greater cytotoxicity for DOX-loaded nanocarriers compared with free DOX, with MNP-HTCC1 showing the strongest effect. Overall, these HTCC-based magnetic nanocarriers offer efficient loading, controlled pH-triggered DOX release, and enhanced therapeutic performance. Full article

Bacterial carbonic anhydrases (CAs) are essential for intracellular pH regulation, bicarbonate homeostasis, and energy metabolism, making them attractive antimicrobial targets. Here, building on evidence that acetazolamide (AZA) delivered via hyaluronic acid–palmitate (HA-PA) nanocarriers impairs Escherichia coli growth and its glucose uptake, we investigated the physiological roles of β- and γ-class CAs using sulphonamide inhibitors with distinct selectivity encapsulated in HA-PA nanomicelles to ensure intracellular delivery. AZA, a potent dual β/γ-CA inhibitor, ethoxzolamide (EZA), a selective β-CA inhibitor, and hydrochlorothiazide (HCT), a weaker inhibitor of both classes, were tested for effects on bacterial physiology. The nanoparticles reduced growth in a dose- and class-dependent manner, with AZA exerting the strongest activity, EZA intermediate inhibition, and HCT only modest effects at higher concentrations. Early metabolic responses assessed via intracellular ATP after three hours of exposure revealed an unexpected and reproducible ATP increase for all inhibitors relative to untreated cells, suggesting reduced ATP consumption in bicarbonate-dependent pathways. These findings provide indirect yet compelling evidence that β- and γ-class CAs influence bacterial energy homeostasis and support the rationale for CA inhibition as an antimicrobial strategy, while highlighting HA-PA carriers as effective systems for delivering CA inhibitors intracellularly and enhancing their functional activity in bacterial cells. Full article

Rheumatoid arthritis (RA) is frequently accompanied by depression, a comorbidity arising from the interplay of chronic systemic inflammation, neuroimmune activation, oxidative stress, and dysregulation of the gut–brain axis. Increasing evidence suggests that nanomedicine offers unique opportunities for the integrated management of RA-associated depression by enabling precise modulation of both peripheral inflammation and central nervous system (CNS) pathology. This review outlines the biological mechanisms linking RA and depression—including cytokine cascades, mitochondrial dysfunction, reactive oxygen species (ROS) accumulation, and microbial metabolite imbalance—and highlights recent progress in nanocarrier platforms capable of dual-site intervention. Liposomes, polymeric nanoparticles (NPs), exosomes, inorganic nanozymes, and emerging carbon-based nanomaterials have demonstrated the ability to target inflamed synovium, reprogram macrophage phenotypes, traverse the blood–brain barrier (BBB), suppress microglial overactivation, enhance neuroplasticity, and restore gut microbial homeostasis. Furthermore, stimulus-responsive nanoplatforms activated by ROS, pH, enzymes, or hypoxia provide spatiotemporally controlled drug release, thereby improving therapeutic precision. Finally, we discuss integrative designs such as dual-targeting nanomedicines, co-delivery systems, and microbiota-modulating nano-interventions, which offer promising strategies for the comprehensive treatment of RA-associated depression. This review aims to provide mechanistic insights and design principles to guide the development of next-generation nanomedicine for coordinated systemic-central modulation in RA comorbidity. Full article

Antimicrobial peptides have been increasingly recognized as potential anticancer agents, with the KLA peptide (KLAKLAK₂) being one of the most well-known and successful examples. The research interest in the KLA peptide is attributed to its ability to induce apoptosis in cancer cells by disrupting the mitochondrial membrane. However, the KLA peptide exhibits poor cellular uptake and it lacks targeting specificity, limiting its clinical potential in cancer therapy. In this review, recent advances in nano-engineered delivery platforms for overcoming the limitations of KLA peptides and enhancing their anticancer efficacy are discussed. Specifically, various nanocarrier systems that enable targeted delivery, controlled release and/or improved bioavailability, including pH-responsive nanosystems, photo-chemo combination liposomes, self-assembled peptide-based nanostructures, nanogel-based delivery systems, homing domain-conjugated KLA structures, inorganic-based nanoparticles, and biomimetic nanocarriers, are highlighted. Additionally, synergistic strategies for combining KLA with chemotherapeutic agents or immunotherapeutic agents to overcome resistance mechanisms in cancer cells are examined. Finally, key challenges for the clinical application of these nanotechnologies are summarized and future directions are proposed. Full article

Background: Tumor-lysate vaccines can capture tumor heterogeneity; however, their effectiveness may be reduced by antigen instability and short antigen presentation. Here, we aimed to improve antigen protection and prolong presentation by using a slow-degrading polymeric nanocarrier and an approved adjuvant. Methods: We encapsulated breast cancer cell lysates (MCF-7 and MDA-MB-231) in poly(ε-caprolactone) (PCL) nanoparticles using a double-emulsion (w/o/w) method and co-administered them with alum. We then characterized particle size, PDI, zeta potential, morphology, and in vitro release. Next, we evaluated nitric oxide (NO), TNF-α/IL-10 responses, and cytocompatibility in J774 macrophages. Finally, we quantified serum antibody titers in Balb/c mice after six biweekly immunizations, generated hybridomas, purified IgG, and tested antibody-mediated cytotoxicity alone and together with doxorubicin. Results: PCL nanoparticles were ~220–255 nm (PDI 0.10–0.19; ζ −2 to −3 mV) and released ~90–95% of encapsulated lysate by 800 h (~33 days). Encapsulated lysate (40 μg/mL) modestly increased NO versus control and increased further with alum (p < 0.05). TNF-α increased 7.4–9.72-fold, whereas IL-10 rose 2.82–3.11-fold. Importantly, encapsulated antigen + alum produced the highest ELISA responses after the sixth dose (6.36-fold for MCF-7 and 7.00-fold for MDA-MB-231 versus control; p < 0.05). Hybridoma-derived antibody signals increased through day 42, and Protein G purification yielded up to ~395 μg and ~318 μg IgG. Purified antibodies reduced cell viability, and viability decreased further when antibodies were combined with doxorubicin (to ~31.6% in MCF-7 and ~40.3% in MDA-MB-231). Conclusions: Overall, sustained PCL-mediated antigen release combined with alum strengthened humoral responses to tumor lysate and enabled recovery of functional antibodies with diagnostic capture and in vitro cytotoxic activity. In future work, key mechanistic steps such as lymph-node trafficking and cross-presentation should be tested directly. Full article

Background/Objectives: Cancer is a major health concern involving abnormal cell growth. Combining anticancer agents can enhance efficacy and overcome resistance by targeting multiple pathways and creating synergistic effects. Methods: This study used in silico approaches to evaluate the physicochemical and pharmacokinetic profiles of the innovative organoselenium nucleoside analog Di3a, followed by the design of two nanocarriers. Di3a-loaded PLGA nanocapsules and nanostructured lipid carriers based on compritol were prepared and evaluated alone and combined with doxorubicin (DOX) and docetaxel (DTX) for a synergistic effect. Results: Di3a subtly violated some of Lipinski’s rules, but still showed suitable pharmacokinetic properties. Both nanoparticles presented nanometric size, negative zeta potential and polydispersity index values < 0.20. Hemolysis assay suggested a pH-dependent pattern conferred by the surfactant 77KL, and evidenced the biocompatibility of the formulations, aligning with the results observed in the nontumor L929 cell line. The lack of drug release studies under varying pH conditions constitutes a limitation and warrants further investigation to validate the pH-responsive properties of the nanocarriers. MTT assay revealed that both formulations exhibited significant cytotoxic effects in the A549 cell line. However, neither formulation exhibited marked toxicity toward NCI/ADR-RES, a resistant tumor cell line. Conversely, when combined with DOX or DTX, the treatments were able to sensitize these resistant cells, achieving expressive synergistic antitumor activity. Conclusions: Despite the limitations in the in silico studies, the study highlights the potential of combining the proposed nanocarriers with conventional antitumor drugs to sensitize multidrug-resistant cancer cells and emphasizes the safety of the developed nanoformulations. Full article

Inflammatory bowel disease is a result of inappropriate continuous non-specific inflammation in the intestinal tract, which in turn is aggravated by defects in the activation of the mucosal immune system and in the barrier function of the intestinal epithelium. The most prominent manifestations of IBD are ulcerative colitis (UC) and Crohn’s disease (CD). UC is characterized by a continuous pattern that commonly starts with lesions in rectum mucosa and is contained in the colon. On the other hand, CD affects the ileum and colon in a discontinuous pattern, and the lesions are often transmural. Conventional therapies often face limitations such as systemic side effects, poor drug stability, and low site-specificity. In recent years, nanoparticle (NP) systems have emerged as a promising strategy to overcome these challenges, offering improved targeting, controlled release, and enhanced therapeutic efficacy. Several studies have shown that the preferential accumulation of NPs in the inflamed colon is influenced by the pathophysiological changes associated with IBD, including alterations in transit time, pH value, enzymatic activity, microbial composition, and mucus integrity. These disease-specific characteristics provide unique opportunities to design smart and responsive NPs that enhance drug delivery and therapeutic efficacy while minimizing systemic exposure. This work presents an overview of novel technologies based on nanosystems, with the ability to specifically target the affected areas of the GI tract in inflammatory bowel disease. Full article

pH-thermo-responsive polymeric nanoparticles (P-Nps) functionalized with carboxylic (–COOH) and amide (–NH₂) groups were synthesized by emulsion polymerization to obtain two series with varying functional group ratios and morphologies: core–shell and core–concentration gradient. P-Np dispersions were characterized by dynamic light scattering (DLS), electrophoresis (zeta potential, ζ), scanning electron microscopy (SEM), and rheology (viscosity, η) in a temperature range of 25 °C to 60 °C. In general, the results show that P-Nps exhibit average particle diameters ranging from 250 ≤ Dz/nm ≤ 1200, and exhibit high colloidal stability (−46 ≤ ζ/mV ≤ −22) as temperature rises. SEM analysis revealed irregular and different structures as the proportion of functional groups varied, while rheological measurements demonstrated non-Newtonian behavior as the average shear rate increased (0.01 ≤ γ ˙ /s⁻¹ ≤ 100). Their size, stability, and rheological properties depend on the temperature and location of the functional groups. These properties suggest potential applications such as in stimulating fluids in the oil industry. Full article

Background/Objectives: This in vitro study examined the potential enhancement in resistance to accelerated aging in room-temperature vulcanized (RTV) maxillofacial silicone, intrinsically pigmented in two skin tones, through the use of zirconium oxide (ZrO₂) nanoparticles. Methods: A total of 128 disc-shaped specimens were created in rose silk and soft brown shades, each containing zirconium oxide concentrations of 0%, 1%, 2%, and 3% by weight. Color variation (ΔE*) was assessed initially and following 252, 750, and 1252 h of artificial aging, tested with a colorimeter. Surface roughness characteristics (R_a, R_q, R_t) were evaluated before and after 1252 h using atomic force microscopy (AFM). Structural, vibrational, and morphological characteristics were analyzed through X-ray diffraction (XRD), Fourier transform infrared spectroscopy (FTIR), and field emission scanning electron microscopy (FESEM). Results: Non-parametric tests (Friedman, Kruskal–Wallis, and Bonferroni-adjusted paired testing; p < 0.05) indicated that accelerated aging significantly increased ΔE* in all specimens. The addition of ZrO₂ reduced these changes; however, the optimal concentration differed by pigment: 1% for rose silk and 3% for soft brown. The effect on surface roughness depended on pigment type. Higher nanoparticle concentrations generally improved post-aging smoothness in soft brown samples, whereas rose silk showed a more variable response. XRD and FTIR analyses confirmed successful nanoparticle incorporation without altering the fundamental silicone structure, while FESEM demonstrated improved filler–matrix interaction in modified groups. Conclusions: Adjusting ZrO₂ concentration according to pigment type can improve the future color retention and surface characteristics of maxillofacial silicone. Full article